Summary: Scientific American explores how the future of mental healthcare may be impacted by MAPS’ first Phase 3 trial of MDMA-assisted therapy for PTSD, the results of which were published one week ago in Nature Medicine.
In the article, MAPS Founder and Executive Director Rick Doblin, Ph.D., reflects on the success of the study, stating, “I expected this to work, but the big surprise was how statistically significant it was.”
Originally appearing here.
A long-awaited study is making worldwide headlines for finding that the outlawed psychoactive drug MDMA is startlingly effective in treating post-traumatic stress disorder (PTSD). But researchers and study participants say the substance itself, while extremely powerful, catalyzes healing rather than working on its own: MDMA treatment also requires dozens of hours of therapy—before, during and after the drug experience—with professionals whose special training is expensive and intense.
Researchers hope the new study, published this week in Nature Medicine, will help this treatment gain regulators’ approval for clinical use within a couple of years. Many therapists and patients are thrilled: About two thirds of PTSD sufferers do not respond to other treatments. And MDMA had shown tremendous promise in earlier, smaller studies.
The California-based Multidisciplinary Association for Psychedelic Studies (MAPS) funded the new study and has been working toward it—and the ultimate goal of legal MDMA therapy—for decades, says senior author Rick Doblin, founder and executive director of the organization. MAPS conducted a small trial with MDMA in Spain starting in 2000, but Doblin says he first met people who had experimented with the drug for trauma relief in 1984. “I knew from before it was even criminalized [in 1985 in the U.S.] that MDMA had an incredible role for PTSD,” he says. It has taken more than 30 years and $75 million in independent funding to reach this point, and even Doblin is surprised at the results. “I expected this to work,” he says, “but the big surprise was how statistically significant it was.”
The new study—a phase III clinical trial—involved 91 patients across 15 sites who were randomized to receive either MDMA (3,4-methylenedioxy-methamphetamine) or a placebo. Neither the participants nor the researchers knew who had been given the psychoactive drug. The scientists found that 67 percent of PTSD sufferers who had MDMA with an intensive course of psychotherapy no longer qualified for a PTSD diagnosis following the trial, compared with 32 percent of those who received a placebo with psychotherapy. And 88 percent of subjects in the MDMA group experienced a “clinically significant improvement” in symptoms.
“This proves what we knew from the earlier studies but now in a multicenter context,” says David Nutt, a psychiatrist and deputy head of the Center for Psychedelic Research at Imperial College London. He was not involved in the new paper, yet has long endorsed MDMA’s potential to help treat PTSD. In a commentary written to accompany the study, Nutt and Harriet de Wit of the University of Chicago note that animal studies and human brain imaging show why and how MDMA might be useful for processing trauma. Scans in humans demonstrate that the drug appears to dampen the activity of the amygdala—a brain region involved in fear—allowing people to more comfortably revisit and process terrifying or painful memories. Rodent studies indicate MDMA can reopen a “critical window” in brain functioning, Nutt says, allowing the organ to regain the plasticity seen in younger brains that are capable of “learning new behavioral responses.”
“PTSD is a difficult nut to crack—one main reason being that traumas become stuck,” explains Jennifer Mitchell, a neuroscientist at the University of California, San Francisco, and lead author of the study. “But with MDMA, things that had really crystallized become more flexible, and this gives you the chance to shake the tree and let all the nuts fall out.”
The fact that the MDMA therapy took place at 15 different sites spanning the U.S., Canada and Israel is one of the factors that makes this study so powerful, Mitchell says. “If the therapy works at all 15 study sites, in all 15 populations with all 15 therapist teams, then chances are you’re onto something—that it’s not the water in Vancouver or the weather in Israel or some specific therapist in San Francisco,” she says. “The chances are that it’s something to do with the MDMA itself.”
The MAPS team anticipates the U.S. Food and Drug Administration will approve MDMA-assisted psychotherapy by 2023. But that may still seem frustratingly far off to some therapists, as well as PTSD sufferers, who frequently struggle with the condition for decades.
John Reissenweber was drafted into the Vietnam War in 1968, when he was 20 years old. He says he experienced multiple traumas resulting from combat experiences and has suffered from PTSD ever since. Although he endured physical injuries, including two broken eardrums, he says it was the psychological trauma of fighting and “survivor’s guilt” from escaping the conflict alive that caused the most damage.
For the next 50 years, Reissenweber says, he self-medicated with alcohol and cigarettes and suffered from profound anger issues. But he never sought help because he did not think he needed it—a common coping strategy. It was only after Reissenweber’s wife and friends confronted him over his anger issues in an “intervention” that he looked into the MAPS study. “I’ve been carrying this shit for 50 years. And now, at the age of 73, I actually wake up and want to live,” he says.
But it is not solely Reissenweber’s MDMA experience, which took place two years ago, that he credits with changing his behavior and healing his trauma. It is also all the work he says the drug inspired him to undertake: solo sessions of cognitive-behavioral therapy for anger management, group therapy with other veterans and even meditation—none of which he thinks would have helped as much if MDMA had not changed something within him. “My entire relationship with my environment has changed,” Reissenweber says. “I’m learning to enjoy life rather than living on the edge.”
He says the huge amount of time he has committed—48 hours of therapy with MAPS for the MDMA dosing, plus two years of his own “integrative” work following the sessions—is what has made the therapy so effective for him. But that also makes it less realistic for many people. “Healing my trauma has become a full-time job, and I just don’t know how somebody with PTSD, who has been in Iraq or Afghanistan and is only in their 30s, could undertake this if they have a job and have to provide for their family,” Reissenweber says.
However time-intensive MDMA therapy may be, or how controversial the drug is, new approaches to PTSD are desperately needed, says Yair Bar-Haim of Tel Aviv University, who has worked with trauma and PTSD for decades but has never done so with MDMA or MAPS. “Two thirds of PTSD sufferers do not respond to conventional treatments,” he says. “These results are phenomenal. I have honestly never seen such a successful trial.”
Bar-Haim says it is too soon to say if MDMA therapy will prove a broadly useful treatment. “What we need are many more trials with much larger samples,” he says. “And preferably with [U.S. government] funding.”